被套細胞淋巴瘤

Buzzwords → Dx

Diagnostic Criteria

• WHO 5e / ICC 2022: B-cell lymphoma with t(11;14) and cyclin D1 overexpression.
• Variants: classic, blastoid, pleomorphic, leukemic non-nodal indolent (SOX11-negative).
• In situ mantle cell neoplasia (ISMCN): cyclin D1+ B cells confined to mantle zone — observe.
• Staging: Lugano (Ann Arbor) + GI endoscopy if abdominal symptoms or marrow+ (lymphomatous polyposis).

Workup

• Excisional biopsy with IHC (cyclin D1, SOX11, Ki-67, CD5, CD23, CD20).
• FISH for t(11;14) mandatory; TP53 sequencing (changes management).
• PET-CT + GI endoscopy (high rate of occult GI involvement).
• Marrow biopsy + flow (frequently involved).
• CSF analysis if blastoid / pleomorphic variant or neurologic symptoms.
• MIPI score + Ki-67 for risk.
• CBC, LDH, β2-microglobulin, HBV/HCV/HIV, echo.

Treatment Algorithm

flowchart TD
  A[Confirmed MCL] --> B{Phenotype}
  B -- leukemic non-nodal<br>SOX11-, IGHV-mutated --> C[Watch and wait if asymptomatic]
  B -- classic / nodal --> D{TP53 mutated?}
  D -- yes --> E[BTKi + R<br>or BTKi + Ven + R<br>avoid cytarabine intensification<br>early allo-HCT consideration]
  D -- no --> F{Age / fitness}
  F -- young, fit --> G[R-DHAP / R-Hyper-CVAD / Nordic<br>+ ASCT consolidation<br>OR BTKi + chemo per TRIANGLE]
  F -- older / unfit --> H[BR or R-CHOP<br>+ rituximab maintenance<br>+ ibrutinib per SHINE]
  G --> I[Maintenance rituximab × 3 yr<br>± ibrutinib post-ASCT TRIANGLE]
  H --> J{Relapse / refractory?}
  I --> J
  E --> J
  J -- BTKi-naive --> K[Zanubrutinib / acalabrutinib / ibrutinib]
  J -- post-BTKi --> L[Pirtobrutinib non-covalent BTKi<br>or brexu-cel CAR-T<br>or Ven combinations]

Pearls / Pitfalls

• TP53-mutated MCL is chemo-resistant — don't intensify with cytarabine + ASCT; pivot to BTKi-based therapy and consider early allo-HCT.³
• TRIANGLE trial (2022) showed adding ibrutinib to R-DHAP induction + ASCT or omitting ASCT (with ibrutinib) gives superior outcomes — challenges traditional ASCT-mandatory paradigm in young MCL.
• Leukemic non-nodal MCL (SOX11-) is the indolent variant — peripheral lymphocytosis + spleen, NO nodal disease, IGHV-mutated. Watch and wait if asymptomatic.
• Brexu-cel CAR-T (ZUMA-2) approved for R/R MCL post-BTKi; high CR rates (~67 %); CRS/ICANS standard.
• Pirtobrutinib (non-covalent BTKi) effective post-ibrutinib (covalent BTKi-resistance via C481S).
• GI involvement is common — consider colonoscopy/EGD at diagnosis if symptomatic; lymphomatous polyposis is the classic MCL GI manifestation.
• CNS prophylaxis considered for blastoid/pleomorphic variants and high-risk MIPI-c — HD-MTX systemic preferred.
• R-maintenance (every 2–3 mo × 3 yr) prolongs PFS post-ASCT (LYMA trial).
• Older patients (R-CHOP era): SHINE trial showed adding ibrutinib to BR + R-maintenance prolonged PFS but with more AEs — risk-benefit case-by-case.
• MCL second cancers: acalabrutinib has lower atrial fibrillation rates than ibrutinib; zanubrutinib also favorable. Check ECG + BP regularly.

Cross-references

• Cytogenetics Atlas — t(11;14) MCL vs t(11;14) MM
• Staging — MIPI, MIPI-c
• Drug Regimens — R-DHAP, BR, BTKi, brexu-cel
• brexu-cel ZUMA-2 CAR-T
• CLL — t(11;14) overlap edge cases

相關題目

• Q-043 — MCL — TP53 mutation impact on therapy
• Q-044 — MCL — leukemic non-nodal indolent variant
• Q-045 — MCL — relapsed disease post-BTKi

Sources